The lymph node is a site where it allows lymphocytes to interact with antigens and antigen-presenting cells to initiate antigen-specific immune responses (adaptive immunity) by assuming a highly organized three-dimensional structure, and is an essential organ for body defense.
The present inventors demonstrated that on the assumption of stromal cells, a cytokine and a polymeric biomaterial as the three essential components for the construction of an artificial lymph tissue, by incorporating stromal cells and a cytokine to a three-dimensional structure configured with a polymeric biomaterial, and transplanting this assembly under the renal capsule of a mouse, a tissue structurally similar to secondary lymph tissue (artificial lymph node) can be constructed 3 weeks after transplantation, and that by adding bone marrow-derived activated dendritic cells to this combination of the three components, the efficiency of artificial lymph node construction can be improved (about 60 to 80% of transplanted tissue) (see JP-A-2004-255110 and Sachiko Suematsu and Takeshi Watanabe, Nature Biotechnology vol. 22, 1539-1545, 2004). The present inventors also succeeded in providing an artificial lymph node that produces an antigen-specific antibody capable of inducing efficient adaptive immune responses in immunodeficient individuals (JP-A-2006-129839). These artificial lymph nodes exhibit functions equivalent to those of innate lymph nodes in vivo. The artificial lymph node described in JP-A-2004-255110 is characterized in that a T cell region and a B cell region are present with distinct separation as in ordinary lymph nodes, and that regarding the ratio of CD4T cells and CD8T cells in the artificial lymph node, CD4T cells account for the majority, this ratio being similar to the ratio of CD4T cells and CD8T cells in the T cell region of normal lymph nodes. The artificial lymph node described in JP-A-2006-129839 is characterized in that along with T cells and B cells, dendritic cells, which play an important role in immune responses, are present, that a B cell region comprising a network of follicular dendritic cells is present in the central portion thereof, that germinal center B cell-like B cells are present, that plasma cells which are antibody-producing cells are present, and the like.
Meanwhile, various immunotherapies have been attempted in cancer treatment; for example, vaccination using a cancer peptide antigen, vaccination using a cancer protein antigen, various cellular therapies using IL-2 activated lymphocytes, NKT cells, dendritic cells and the like, cytokine therapy, antibody preparations, BRM non-specific immunotherapy using cell body components of BCG or tubercle bacillus and the like, and the like are known, but to obtain persistent immunostimulatory effects in vivo, these therapies need to be applied a plurality of times.